Reduction of linezolid-associated thrombocytopenia by the dose adjustment based on the risk factors such as basal platelet count and body weight

The aim of the present study was to evaluate the efficacy of dose modification based on the risk factor for linezolid-induced thrombocytopenia. A multivariate logistic regression analysis performed in the observational study showed that low body weight of <55 kg (odds ratio [OR]: 33.2, 95% confidence interval [CI]: 2.16–510.1, P = 0.012) and the baseline platelet count of <200 × 10³/mm³ (OR: 24.9, 95% CI: 1.53–404.7, P = 0.024) were found to be risk factors for linezolid-induced thrombocytopenia. In the subsequent intervention study, in which daily dose of linezolid was set to 20 mg/kg in patients with either one of the risk factors or 1200 mg in those without any risk factor, the onset of thrombocytopenia was significantly prolonged in the intervention study group (P = 0.043), without reducing clinical efficacy. These findings suggest that dose adjustment of linezolid is effective in preventing thrombocytopenia without reducing its clinical efficacy in patients having risk factors.     

Impact of patient characteristics and infection type on clinical outcomes of patients who received linezolid or vancomycin for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: a pooled data analysis

Phase III randomized, clinical trials are primarily designed to evaluate overall treatment-outcome comparisons. Although valuable data are gained from such comparisons, it is difficult to draw meaningful inferences about potential outcomes differences in specific patient groups and infection types. It is well established that clinical outcomes are dependent on host, treatment- and pathogen-related factors and understanding which groups benefit from one treatment relative to another is of great importance. This study sought to determine if clinical success in the treatment of complicated skin and skin structure infections (cSSSI) caused by methicillin resistant Staphylocccus aureus (MRSA) with linezolid or vancomycin varied across subpopulations and infection type. Data from 3 prospective, randomized trials evaluating linezolid and vancomycin for the treatment of MRSA cSSSI were pooled. Treatment related differences in outcomes were found, on both the absolute and relative scales, for most subpopulations and infection types. Identifying treatment differences in outcome by patient subpopulation can enhance clinical decision making.     

强化期利奈唑胺替代乙胺丁醇治疗药物敏感肺结核的临床效果观察

目的 探讨在抗结核标准治疗方案中使用利奈唑胺代替乙胺丁醇方案治疗药物敏感肺结核的效果.方法 将2018年1月—2020年7月在盘锦市传染病医院就诊的43例药物敏感肺结核患者随机分为对照组和利奈唑胺组.对照组给予标准抗结核方案治疗.利奈唑胺组使用利奈唑胺替代标准抗结核治疗方案中的乙胺丁醇进行治疗.比较两组的治疗效果、治疗...     

Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as ‘probable’ on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.     

In-vitro activity of ceftriaxone combined with newer agents against MRSA

In this study, in vitro synergism in combinations of agents as ceftriaxone/dalbavancin, ceftriaxone/linezolid and ceftriaxone/daptomycin against MRSA strains were investigated. Thirty clinical MRSA strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using reference broth microdilution method. In-vitro activities of antibiotics combined against the strains were tested using two-dimensional checkerboard microdilution method. Results were interpreted as follows: synergy = FICI ≤0.5; ‘no interaction’ effect = FICI ?0.5-≤4; antagonism = FICI ?4. The MIC₅₀, MIC₉₀ and MIC_range of ceftriaxone, daptomycin, dalbavancin and linezolid were found as 128, 1024 and 16-2048 mg/L; 1, 1 and 0.5–1 mg/L; 0.12, 0.12 and 0.03–0.12 mg/L; and 1, 2 and 1–2 mg/L, respectively. Our results showed that the frequency of synergistic effects (FICI: ≤0.5) of three combinations were all at the same rate of 77% (23/30). No in vitro antagonism (FICI >4) was observed.     

Early experience with linezolid for infections in orthopaedics

In infections following orthopaedic surgery, isolated staphylococci are reported to be methicillin resistant (MRSA) in up to 50% of cases. Linezolid, the first in a new class of antibiotics, has excellent efficacy against gram positive organisms that are resistant to other therapies and is 100% orally bioavailable. We report early results of its use for the treatment of resistant infections in orthopaedic practice. Infections were characterised according to the UK Nosocomial Infections National Surveillance Service classification of surgical infections as superficial, deep or organ/space. Osteomyelitis, joint sepsis and deep infection involving orthopaedic implants were included into the final category. Outcome was recorded as clinical, microbiological and blood parameter cure or fail. Over the 12-month study period, 54 patients received linezolid therapy, 41% of these had significant co-morbidity that might affect their ability to fight infection. Sixty-seven percent of infections were in association with implanted metal work. The majority of patients were treated with vancomycin for a short period before linezolid was used as oral 'switch' therapy for longer-term administration, allowing early discharge in all cases. MRSA was isolated in 87% of the patients treated. The mean length of linezolid therapy was 39 days (2-151). Clinical success was achieved in 90% of patients overall. Though there were no life-threatening complications, adverse event rates were significantly higher than those recorded in the literature, with 19% of patients needing to cease therapy. Linezolid offers an alternative to traditional treatments for resistant infections and can facilitate early discharge. Patients need to be monitored closely, particularly where long-term therapy is planned.     

Activities of clindamycin,synercid, telithromycin,linezolid, and mupirocin against gram-positive coccal strains resistant to erythromycin in korea

The antibacterial activities of clindamycin, synercid, telithromycin, linezolid and mupirocin were evaluated against erythromycin-resistant Gram-positive coccal clinical isolates collected in Korean hospitals. In Staphylococcus aureus, synercid, linezolid and mupirocin were the most active agents. Against coagulase-negative staphylococci (CNS), synercid, linezolid and mupirocin were also active. Telithromycin and synercid resistance was common against enterococci, only linezolid and mupirocin were active. The reason of low activity of telithromycin against staphylococci and enterococci is because most of the isolates were constitutively resistant to erythromycin. Synercid, telithromycin, linezolid and mupirocin were active against streptococci.     

对1例骨折截肢术后老年患者使用利奈唑胺的药物监测

1例70a女性患者,因右股骨远端骨折合并双下肢动脉硬化闭塞症、高血压、类风湿性关节炎入院。入院后由于右足感染不能控制,行右大腿上段截肢术。术后合并血流感染和肺内感染,根据细菌培养结果,给予利奈唑胺600mg,q12h,ivgtt。3d后患者出现转氨酶ALT、AST分别升高至163IU·L-1、541IU·L-1,白细胞和血小板减少,遂将利奈唑胺剂量调整为400mg,q12h,ivgtt,后转氨酶恢复正常。停药后,白细胞和血小板恢复正常。     

静脉滴注利奈唑胺致白细胞及中性粒细胞减少1例

1例57a女性患者,既往患慢性肾功能衰竭,行持续不卧床腹膜透析治疗。因急性腹膜炎静脉滴注利奈唑胺0.6g,bid。用药2d后,出现白细胞及中性粒细胞减少,WBC2.43×109·L-1,N0。立即停药,给予粒细胞集落刺激因子100μg对症治疗。2d后复查血常规WBC9.10×109·L-1,N41.6%。之后换用其他抗菌药物,未出现白细胞及中性粒细胞减少。     

利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

目的：比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度（MPC）和最低抑菌浓度（MIC）的相关性。方法：采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌（MRSA）临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利夺唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果：利奈唑胺、万古霉素对35株MRSA的MPC90值（抑制90％的细菌发生细菌耐药的最低防耐药突变体选择浓度）分别为16.8μg／mL,选择指数（MPC90／MIC90）均为8。两药对MRSA的MPC和MIC的线性相关系数R^2分别为0．32和0．008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论（MSW）中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论：万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。